Overexposure to the sun's invisible rays, ultraviolet A (UVA, 320-400 nm) and ultraviolet B (UVB, 290-320 nm) can cause skin damage. The damage can be immediate and long-term, with effects ranging from sunburn, rashes, and cell and tissue damage to premature wrinkling and skin cancer. One particularly deadly form of skin cancer, malignant melanoma, has been on the rise in recent decades, as tanning has become more popular. Over the same period, scientists have warned that the thin layer of ozone that protects life on Earth from the sun's ultraviolet (UV) radiation is being depleted. This allows more UV radiation to get through, adding to the risk of overexposure. Indeed, many skin changes that often are identified with aging actually result from damage by too much sun.
Sunscreen is any substance or material that protects the skin from UV radiation. Sunscreens are available in the forms of topical lotion, cream, ointment, gel, or spray that can be applied to the skin; a salve or stick that can be applied to the lips, nose, and eyelids; a moistener in towelettes that can be rubbed against the skin; sunglasses that protect the eyes; and film screen that can be affixed to the windows of a car, room, or office.
Sunscreens help to prevent sunburn and reduce the harmful effects of the sun such as premature skin aging and skin cancer. But just how much protection they provide is a matter of debate. For many years, experts thought that only UVB was harmful. However, recent research suggests that UVA may be just as dangerous as UVB, although its effects may take longer to show up. In particular, UVA may play a role in causing melanoma. Most sunscreen products contain ingredients that provide adequate protection only against UVB rays. Even those labeled as “broad spectrum” sunscreens may offer only partial protection against UVA radiation. Those containing the ingredient avobenzone (4-tert-butyl-4′-methoxydibenzoylmethane) give the most protection against UVA rays.
Sunscreens should be applied between 30 minutes and 2 hours before sun exposure. In general, they should be reapplied after every 80 minutes spent in the water or when perspiring heavily or every 2 hours spent out of the water.
UVB (290-320 nm) is the most erythemogenic solar radiation reaching the surface of the earth. It is also a potent skin carcinogen in animal studies. Sun Protection Factor (SPF) indicates the degree of protection against UVB induced erythema. The US Food and Drug Administration (FDA) regulates sunscreen products as over-the-counter drugs. The Final Over-the-Counter Drug Products Monograph on Sunscreens (Federal Register 1999:64:27666-27963) established the conditions for safety, efficacy, and labeling of these products. The SPF is defined as the dose of ultraviolet radiation (UVR) required to produce 1 minimal erythema dose (MED) on protected skin after the application of 2 mg/cm2 of product divided by the UVR required to produce 1 MED on unprotected skin.
All sunscreens have a SPF on their labels. The SPF represents the length of time that sunscreen-protected skin can be exposed to UV rays before a minimal redness (erythema) appears, compared to the length of time it takes on unprotected skin. In other words, it indicates how much longer the skin can be exposed to the sun before getting a sunburn. For example, without a sunscreen, an individual might get a sunburn after 20 minutes or less in the sun. By applying a sunscreen of SPF 15, the individual might spend up to 300 minutes under the sun before sunburning, that is 15 times longer than if no protection is used.
Sunscreens with SPF numbers higher than 15 may work better for people who are fair-skinned, live at high altitudes, work or play outdoors much of the day; or perspire heavily. Swimming and perspiration reduce the actual SPF value of many sunscreens, even those that are water-resistant, so it is convenient to reapply the product often.
Table 1 shows some relevant broadly used sunscreen compounds.
TABLE 1Drug NameConcentration %AbsorbanceProtection nmAvobenzone2-3UVA I1320-400DioxybenzoneUp to 3UVB, UVA II2250-390OxybenzoneUp to 6UVB, UVA II2270-350SulisobenzoneUp to 10UVB, UVA II2260-3751340-400 nm;2320-340 nm
Avobenzone (4-tert-butyl-4′-methoxydibenzoylmethane, Parsol 1789, U.S. Pat. No. 4,387,089) provides superior protection through a large portion of the UVA range, including UVA I. Potentially a significant addition to sunscreen products for true broad-spectrum UV protection, concerns have been raised regarding its photostability and its potential to degrade other sunscreen ingredients in products in which it is used.
Dioxybenzone (2,2′-dihydroxy-4-methoxybenzophenone, U.S. Pat. No. 2,853,521) is mainly used as an UV-absorber for polymers and coatings. It is used as a stabilizer for polyester film. It is effective against UVB and some UVA light.
Oxybenzone (2-hydroxy-4-methoxybenzophenone, U.S. Pat. No. 2,773,903, U.S. Pat. No. 2,861,104, U.S. Pat. No. 2,861,105 and U.S. Pat. No. 3,073,866) absorbs well through UVA II and can be considered a broad-spectrum absorber. It significantly enhances UVB protection when used in a given formula.
Sulisobenzone (5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid, GB1136525) extends the coverage beyond the UVB range and into the UVA range, helping to obtain broad-spectrum sunscreen preparations.
Amino-substituted hydroxybenzophenones have been disclosed as photostable UV filters to be used in cosmetic and dermatological compositions (U.S. Pat. No. 6,409,995).
Chemical sunscreens “block” the penetration of UV radiation through the epidermis by acting as filters and absorbing and reflecting high energy UV. The sunscreen molecules absorb the high energy UV photons causing the electronic structure to move to a higher energy state. This electronic energy is dissipated by conversion to vibrational and rotational energy within the molecule, ultimately being transferred to the molecule's environment as heat.
The FDA has taken a position against the continued labeling of high SPF formulations, and has stated that the maximum SPF should not exceed 30 due to the additional costs and risks from increased concentrations of active ingredients. This is in spite of the fact that other than the expected occurrence of occasional allergic, phototoxic, and photoallergic cutaneous reactions, there is virtually no published evidence of harm from using high SPF sunscreen formulations.
There are, in fact, a number of reasons why high SPF formulations (>30 SPF) may be the best choice for high risk individuals, especially when sun exposure is expected to be extensive. Rubbing, sweating, and water immersion diminish the effectiveness of all sunscreens, requiring frequent re-application of the product even with supposedly waterproof or sweat proof formulations. Another factor that enhances the damaging effects of lengthy exposures is a time-dependent diminution of SPF effect not related to removal of the product from rubbing or washing. Experiments in the hairless mouse model found a significant decrease in measured SPF occurring within the first few hours following sunscreen application. Studies in humans confirm that single applications of an SPF 25 sunscreen are frequently inadequate to prevent erythema, and that multiple applications are required to completely suppress erythema, even from a single day's sun exposure.
A final factor that may not be fully compensated for, even with repeated application, is the effect of multi-day UV exposures. A significant multi-day exposure to sunlight (e.g., all day Saturday and Sunday) increases the sensitivity of the skin to UV damage on the second day of exposure. This means that even if the sunscreen functions as predicted by the rated SPF to prevent erythema on the first day of exposure, the heightened sensitivity on the second and subsequent days of exposure may lead to erythema development which would not have been predicted based solely on extrapolations of the SPF. In such instances, a sunscreen with an SPF>30 may provide significantly better protection from UV damage, particularly in susceptible individuals.
Higher SPF sunscreen products have led to the use of multiple individual sunscreen agents used in combinations at maximum concentrations that may interact.
The current focus on erythema as the standard against which sunscreen potency is measured may have led to the assumption that erythema prevention is also the only important goal of sun protection, and ultimately to the FDA's position against sunscreens more potent than 30 SPF. This assumption ignores experimental evidence that significant UV-induced damage occurs prior to the development of perceptible UV-induced redness. Human research using sunburn cells as the measure of UV damage supports the existence of significant sub-erythemal DNA damage in the skin, and the value of high SPF sunscreens in preventing it.
SPF testing is designed to evaluate protection against erythema produced by natural sunlight and, therefore, denotes principally the degree of protection against UVB, since the amount of UVA received from sunlight does not produce significant erythema. The only ingredient approved by the FDA for protection against UVA radiation is avobenzone. However, if a product contains ingredients that absorb UV between 290-320 nm it can be labeled as a broad-spectrum sunscreen, meaning it will provide protection against both UVB and short wave UVA radiation.
Adverse reactions to sunscreen comprise cutaneous problems, such as allergic contact reactions, photocontact reactions, and drying or tightening of the skin. Other side effects are rare, but possible, namely acne, burning, itching, or stinging of the skin, redness or swelling of the skin, rash, with or without blisters that ooze and become crusted, pain in hairy parts of body and pus in hair follicles.
Photostability refers to the ability of a molecule to remain intact with irradiation. Poor photostability is potentially a problem with all UV filters because they are deliberately selected as UVR-absorbing molecules. This issue has been raised specifically with avobenzone, with photolysis demonstrated, especially in vitro systems, that simultaneously irradiate and measure transmittance in situ. The photostability of the molecules also depends on the solvent or the vehicle used.
Subjective irritation associated with burning or stinging without objective erythema is the most common sensitivity complaint from sunscreens. This irritation is most frequently observed in the eye area. However, persistent objective irritant contact dermatitis is a more common side effect. Virtually all sunscreen ingredients reported to cause contact allergy might be photoallergens. Sunscreen actives seem to have become the leading cause of photocontact allergic reactions. Individuals with preexisting eczematous conditions have a significant predisposition to sensitization associated with their impaired cutaneous barrier. In addition, certain antibiotics, birth control pills, diuretics, antihistamines, and antidepressants are among the commonly used drugs that can increase sensitivity to the sun's rays.
A water resistance claim of two hours means the sunscreen should retain its full SPF protection even after two hours in the water. Even water resistant, sunscreen should be reapplied after any water sports.
It is therefore desirable to discover new sunscreen compounds with a lower risk of side effects, increased photostability, and increased persistence on the skin.
The present invention provides a method for protecting a human or animal living body from ultraviolet radiation comprising treating said human or animal living body with an effective amount of a composition comprising a benzoic acid ester compound with ultraviolet absorbing properties per se susceptible to be photochemically converted in situ to another sunscreen compound with a higher UV protection. Also the present invention provides a method for protecting a material from ultraviolet radiation comprising treating said material with an effective amount of a composition comprising a benzoic acid ester compound with ultraviolet absorbing properties per se susceptible to be photochemically converted in situ to another sunscreen compound with a higher UV protection.